Transferrin-Coated Gadolinium Nanoparticles as MRI Contrast Agent

Purpose

In this study, the contrasting properties of human serum albumin nanoparticles (HSA-NPs) loaded with gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and coated with transferrin in MRI in mice are evaluated.

Procedures

HSA-NPs were conjugated with Gd-DTPA (Gd-HSA-NPs) and coupled with transferrin (Gd-HSA-NP-Tf). Mice underwent MRI before or after injection of Gd-DTPA, Gd-HSA-NP, or Gd-HSA-NP-Tf.

Results

All the studied contrast agents provided a contrast enhancement (CE) in the blood, heart muscle, and liver. Compared to Gd-DTPA, CE with HSA-NP was achieved at lower Gd doses. Gd-HSA-NP-Tf yielded significantly higher CE than Gd-HSA-NP in the skeletal muscle, blood, cardiac muscle, and liver (p?<?0.05). Gd-HSA-NP-Tf achieved a significantly higher CE than Gd-HSA-NP and Gd-DTPA in the blood, cardiac muscle, and liver (p?<?0.05). In the brain, only Gd-HSA-NP-Tf was found to cause a significant CE (p?<?0.05).

Conclusions

The Gd-HSA nanoparticles have potential as MRI contrast agents. In particular, Gd-HSA-NP-Tf has a potential as a specific contrast agent for the brain, while the blood–brain barrier is still intact, as well as in the heart, liver, and skeletal muscle.     

Attenuation of oxidative stress-induced neuronal cell death by Hydnophytum formicar-um Jack.

Objective: To investigate protective effects of Hydnophytum formicarum Jack.(H. formicarum) extracts via regulation of SIRT1-FOXO3a-ADAM10 signaling and antioxidant activity against H_2O_2-induced neurotoxicity in neuroblastoma SH-SY5Y cells. Methods: Cell viability and apoptosis of neuronal cells pretreated with H. formicarum Jack. extracts under oxidative stress were determined by MTT assay and flow cytometry. The intracellular reactive oxygen species(ROS) was performed using Carboxy-DCFDA assay. Additionally, a profile of protein expressions related to neuroprotection was detected by western blot analysis. Results: The plant extracts(methanol and ethyl acetate) elicited protective effects on the neuronal cell death as performed by the MTT assay and by apoptosis analysis via the activation of BCL-2. Both ethyl acetate and methanol extracts exerted inhibitory effects against H_2O_2-induced ROS generation in the SH-SY5Y cells. Furthermore, the possible mechanism of neuroprotection of H. formicarum Jack. was observed through its antioxidant properties by maintaining the levels of catalase and SOD2 proteins as well as activating SIRT1-FOXO3a pathway. Importantly, pretreatment of neuronal cells with H. formicarum Jack. significantly recovered the levels of ADAM10 protein compared with the H_2O_2 treatment alone. Conclusions: The recent findings suggest the protective effects of H. formicarum Jack. plant extracts on attenuating H_2O_2-induced neurotoxicity in human SH-SY5Y cells.     

Butein,isoliquiritigenin, and scopoletin attenuate neurodegeneration via antioxidant enzymes and SIRT1/ADAM10 signaling pathway

Neuronal cell death is a key feature of neurodegenerative disorders such as Parkinson''s and Alzheimer''s diseases. Plant polyphenols, namely butein, isoliquiritigenin, and scopoletin, have been shown to exhibit various biological activities including anti-inflammatory, antimicrobial, and antioxidant activities. Herein, butein, isoliquiritigenin, and scopoletin were explored for their neuroprotective properties against oxidative stress-induced human dopaminergic SH-SY5Y cell death. The cells exposed to hydrogen peroxide (H₂O₂) revealed a reduction in cell viability and increases in apoptosis and levels of reactive oxygen species (ROS). Interestingly, pretreatment of SH-SY5Y cells with 5 μM of butein, isoliquiritigenin, or scopoletin protected against the cell death induced by H₂O₂, and decreased the levels of apoptotic cells and ROS. In addition, the levels of SIRT1, FoxO3a, ADAM10, BCL-2, and antioxidant enzymes (catalase and SOD2) were maintained in the cells pretreated with butein, isoliquiritigenin, or scopoletin before H₂O₂ treatment compared to cells without pretreatment and the reference (resveratrol). Molecular docking analysis revealed that the interactions between the activator-binding sites of SIRT1 and the phenolic compounds were similar to those of resveratrol. Taken together, the data suggest that these polyphenolic compounds could be potential candidates for prevention and/or treatment of neurodegeneration.

Neuronal cells exposed to H₂O₂ may undergo increase ROS, reduction in cell viability and cell death. Butein, isoliquiritigenin, and scopoletin ameliorated H₂O₂-induced neurotoxicity by reducing ROS, balancing antioxidants and activating SIRT1-FoxO3a-ADAM10 pathway.     

High-frequency QRS electrocardiogram predicts perfusion defects during myocardial perfusion imaging

BACKGROUND: Changes in high-frequency (HF) QRS components of the electrocardiogram (ECG) (150-250 Hz) are more sensitive than changes in conventional ST segments for detecting myocardial ischemia. We investigated the accuracy of 12-lead HF QRS ECG in detecting perfusion defects during adenosine tetrofosmin myocardial perfusion imaging (MPI). METHODS AND RESULTS: 12-lead HF QRS ECG recordings were obtained from 45 patients before and during adenosine technetium Tc 99m tetrofosmin MPI tests. Before the adenosine infusions, recordings of HF QRS were analyzed according to a morphologic score that incorporated the number, type, and location of reduced amplitude zones (RAZs) present in the 12 leads. During the adenosine infusions, recordings of HF QRS were analyzed according to the maximum percentage changes (in both the positive and negative directions) that occurred in root mean square voltage amplitudes within the 12 leads. The best set of prospective HF QRS criteria had a sensitivity of 94% and a specificity of 83% for correctly identifying the MPI result. The sensitivity of simultaneous ST-segment changes (18%) was significantly lower than that of any individual HF QRS criterion (P < .001). CONCLUSIONS: Analysis of 12-lead HF QRS ECG is highly sensitive and reasonably specific for detecting perfusion defects during adenosine MPI stress tests and significantly more sensitive than analysis of conventional ST segments.     

Investigation of memory responses following <Emphasis Type="Italic">Plasmodium chabaudi</Emphasis> AS infection in mice distinct in susceptibility to clinical malaria

Plasmodium chabaudi chabaudi AS blood stage infection results in various degrees of clinical symptoms to malaria depending on the mouse strain. This study aimed to investigate the development of memory responses in susceptible A/J and resistant C57BL/6 mice which differ in the degree of susceptibility to clinical malaria following P. chabaudi AS infection. A rapid increase of activated cells (CD25⁺, CD44^high, and CD62L^low) and production of both interferon-γ and interleukin-4 was found in spleens of both malaria-infected mouse strains. After the parasitemia had been cleared, these activated cells were converted to their resting phenotypes. Although exhibiting susceptible phenotype and having lower magnitude of cellular changes during primary infection, susceptible A/J mice that had been exposed to malaria parasites and drug-cured were able to generate protective immunity capable of control parasite growth following reinfection to the same level as C57BL/6 mice. This may be due to the capability of susceptible mice to produce parasite-specific antibodies, in particular of the IgG2a and IgG3 isotypes. The results from this study may provide more insights useful for the development of vaccines against malaria.     

Dye wastewater treatment enabled by piezo-enhanced photocatalysis of single-component ZnO nanoparticles

Conventionally, composite materials are usually employed as a catalyst in piezo-photocatalytic dye wastewater treatment. Here, we report the synthesis of ZnO nanoparticles, as a single-component catalyst, by surfactant-assisted precipitation in which the size of ZnO nanoparticles (20–100 nm) can be simply controlled by the use of Tween80 as a surfactant. Although, ZnO nanoparticles exhibited appreciable photocatalytic activities for the degradation of methylene blue (MB) dye, upon the addition of a mechanical force, the photocatalytic dye degradation efficiency was substantially improved. Furthermore, we postulated that the surface properties of ZnO play an important role in charge transfer phenomena based on photoluminescence results together with functional groups on the surface of ZnO. In addition, application of single-component ZnO in piezo-promoted photocatalytic degradation of cationic and anionic dyes was accomplished. Our results regarding the behaviour of single-component ZnO nanoparticles under vibrational energy in addition to their conventional solar harvesting can provide a promising strategy for developing photocatalysts for practical wastewater treatment.

Single-component ZnO nanoparticles, synthesized by a simple synthetic method, exhibit appreciable piezo-enhanced photocatalytic activities, representing an alternative to other complex systems.     

T-SPOT®.TB test and clinical risk scoring for diagnosis of latent tuberculosis infection among Thai healthcare workers

BackgroundScreening for latent tuberculosis infection (LTBI) is important to identify healthcare workers (HCWs) benefiting from preventive therapy. Interferon-gamma release assays (IGRAs) are sensitive and specific tests for LTBI diagnosis. However, in settings where IGRAs are not available, clinical risk assessment may be used as an alternative to diagnose LTBI.MethodsA cross-sectional study was conducted among HCWs of a tertiary-care university hospital in Thailand. All HCWs underwent T-SPOT®.TB test (T-SPOT) and assessment of LTBI clinical risks. Clinical risks associated with T-SPOT positivity were determined by multivariable logistic regression analysis and were given scores accordingly. The performance of the clinical risk scoring was evaluated in comparison to T-SPOT.ResultsAmong 140 enrolled HCWs, 125 (89%) were females, the median age was 27 years and 23 (16%) had T-SPOT positivity. Independent factors associated with T-SPOT positivity were age ≥30 years (adjusted odds ratio [aOR] 3.95; P = 0.002), working duration ≥60 months (aOR 3.75, P = 0.004) and frequency of TB contact ≥6 times (aOR 8.83, P = 0.005). The study's clinical risk scoring had the area under the curve by receiver operating curve analysis of 0.76 (P < 0.001) using T-SPOT positivity as a reference standard. The score of ≥3 had the best performance in diagnosing LTBI with sensitivity, specificity, positive predictive value and negative predictive value of 70%, 71%, 32% and 92%, respectively.ConclusionsIn this setting where LTBI was prevalent among HCWs but IGRAs are not widely available, the clinical risk scoring may be used as an alternative to diagnose LTBI in HCWs.